One of the greatest mistakes the sponsor of a 505(b)(2) product can make is to have an unsuccessful pre-IND meeting. Errors often occur at the pre-IND meeting because sponsors and CROs that are more familiar with traditional 505(b)(1) development programs fail to appreciate the different goals and the impact of a pre-IND meeting on a 505(b)(2) program.

The goal of a 505(b)(1) pre-IND meeting is to introduce the FDA to the novel drug, discuss standard toxicology study results, and propose a first-in-human study. In contrast, a properly prepared and conducted 505(b)(2) pre-IND meeting presents the proposed strategy and the entire development program, including the justification for leveraging existing data in place of required studies. Therefore, the approval strategy presented in the 505(b)(2) pre-IND meeting is paramount, requiring productive discussion and alignment with the FDA.

We cannot overemphasize the importance of getting FDA feedback on the entire development program at the pre-IND meeting. The meeting must be successful.

What is pre-IND meeting success?

How does Premier Consulting define a “successful pre-IND meeting”? All too often we are approached by companies that have conducted a do-it-yourself pre-IND meeting. They ask us, “What studies do we need to do?” They say they had a great pre-IND meeting, learned that their product was “likely” a 505(b)(2) candidate, and didn’t get any negative “vibes.” Ouch.

After a pre-IND meeting, Premier Consulting expects that a client will know:

• What studies are needed — the endpoints, measurements, and other information sufficient for a protocol design (not a pharmacokinetics study, but what pharmacokinetics study)
• What the studies should cost, how long they should take, what order they should be conducted in, and what the risks are

In other words, you should come out of a pre-IND meeting with a solid plan. That is success. Anything less is failure.

Preparing for a pre-IND meeting

A pre-IND is a Type B meeting, also known as a milestone meeting. The FDA typically grants only one meeting for each milestone such as pre-IND, end-of-phase, and pre-NDA meetings. This makes the conduct of and preparation for these meetings critical. The sponsor determines the questions it wants the FDA to answer.

An initial version of these questions is sent to the FDA with a meeting request letter that describes the proposed product, including its chemical identity, intended indication, and route of administration. The FDA uses the information to determine whether a meeting will be granted and, if so, which staff will be present. The FDA has the option of granting or denying a meeting, depending on the appropriateness of the questions and the product, or providing written responses in lieu of a meeting.

At Premier Consulting, we believe good preparation for the meeting request is important, as improving the chance of a face-to-face meeting with the FDA is almost always in a sponsor’s best interest. That said, some FDA divisions provide only written responses for almost all pre-IND meeting requests.

As outlined in the Draft Guidance for Industry: Formal Meetings Between the FDA and Sponsors or Applicants of PDUFA Products, a response to the meeting request is usually provided within 21 days, and the FDA aims to schedule the meeting within 60 days of receipt of the meeting request letter. However, with increasing workloads, many divisions are unable to meet this goal.

The sponsor must submit a meeting package that contains the final version of the questions and background information at least one month before the meeting date. Some divisions request the package even earlier. For a product seeking approval via the 505(b)(2) pathway, the package will need to include data from sources other than sponsor studies, with a justification for how and why it can be used to reduce the size of a full development program. The data must be of a standard suitable for the FDA to assess, and the plan to establish a scientific bridge between the drug used in the data and the sponsor’s product must be clearly demonstrated.

What happens in a pre-IND meeting?

A pre-IND meeting usually starts with introductions from the FDA review team, including the division director or a designee, and the sponsor’s representatives. The FDA project manager or the sponsor may then choose to give an introduction or proceed straight to questions.

Typically, the FDA will provide written preliminary responses to the sponsor’s questions within a few hours or days of the formal meeting. The sponsor generally advises the FDA project manager, prior to the meeting, which questions the sponsor would like to discuss and in what order. The selected questions and agency responses are discussed and clarifications provided. The goal is to gain FDA agreement first on the most critical aspects of the development plan and continue through to the most straightforward aspects within the allocated time (usually one hour, but as little as 30 minutes for some divisions).

Dos and don’ts for a pre-IND meeting

From Premier Consulting’s experience interacting with regulatory agencies 75+ times per year, here are some important points for getting the most out of your pre-IND meeting:

Do leave behind the slide presentation. In most cases, a slide presentation from the CEO takes up valuable time without changing the meeting outcome. Sponsor presentations are more typical for a pre-submission meeting with the Center for Devices and Radiological Health but are not a requirement. Within the Center for Drug Evaluation and Research, most divisions do not welcome slide presentations. Go straight to the prepared questions and the discussion of data. You will get more out of your meeting, and the FDA will appreciate the concise nature of the agenda.

Do prioritize carefully. Points on which the FDA agrees with your proposed development plan require less discussion, if any discussion is needed at all, than questions on which there is disagreement. The sponsor can determine which questions are addressed and in which order, so it is important to prioritize the questions in order of importance for discussion in the allotted time.

Do listen to what the FDA is saying. In many cases, the FDA has a unified opinion on how a study should be conducted or how an issue should be addressed. Think about ways to accommodate what the agency is trying to communicate. Countless sponsors pursue their own agenda, despite the FDA advising otherwise, only to end up repeating a study or, worse, stalling the entire program indefinitely.

Do make your point if you have something new to add. In some cases it’s OK to push back if you have a logical justification and the point has not been made adequately in the meeting package, or if additional information has become available. An example is when a new issue arises in the meeting and one of the experts on your team has experience with that issue. But be careful not to continue to push if you have already made your point and the FDA does not agree. The goal is to gain insight into the agency’s requirements for the program, not to reach agreement on every aspect during the meeting.

Don’t forget to watch the time. You get only an hour (or 30 minutes in some cases), so be mindful of how much time any particular issue is worth in relation to the rest of the agenda. The representative the sponsor chooses to lead the meeting should be adept in calling on the subject-matter experts to speak when needed, and on ending the discussion when enough has been said. Rather than debating a minor detail, know when to move on.

It helps to have a good understanding of what the FDA is expecting, and on which points some negotiation is possible. At Premier Consulting, we lead three to six pre-IND meetings per month.

To learn more about how to optimize the pre-IND or pre-submission meeting outcome for your product, or to get advice on your drug/device development program, contact us.

Authors:

Angela Drew, PhD
Product Ideation Consultant

Ken Phelps
Strategic Adviser